[Updates on primary mediastinal large B-cell lymphoma and mediastinal gray zone lymphoma]

Recent advances in molecular pathology have profoundly reshaped the understanding and classification of mediastinal lymphomas, particularly primary mediastinal large B-cell lymphoma (PMBL) and mediastinal gray zone lymphoma (MGZL). These entities, long defined by morphological and immunophenotypic criteria, are now characterized by distinct genetic and transcriptional signatures. PMBL is defined by recurrent alterations involving CIITA, 9p24 (PD-L1/PD-L2), SOCS1, STAT6, and B2M, reflecting constitutive activation of the JAK/STAT and NF-κB pathways. Transcriptomic studies confirm its distinction from non-thymic diffuse large B-cell lymphomas (DLBCL) while revealing molecular overlaps with classical Hodgkin lymphoma (cHL). MGZL, on the other hand, exhibits intermediate and variable morphological and immunophenotypic features between PMBL and cHL, consistent with a shared thymic B-cell origin but divergent differentiation mechanisms. Alterations of PD-L1/PD-L2 have important prognostic implications, while circulating tumor DNA is emerging as a promising, non-invasive biomarker for molecular profiling and disease monitoring. Recent clinical studies have also led to significant therapeutic advances in PMBL, integrating molecular data into tailored treatment strategies and paving the way for precision medicine approaches in mediastinal lymphomas.